CT引导下兔肺内VX2肿瘤的射频消融治疗

背景与目的：外科手术切除、放疗和化疗是治疗肺恶性肿瘤的主要方法,但对失去手术机会、肺内多发转移或放化疗失败的患者,积极探索新的治疗方法成为亟待解决的问题。近年来,射频消融作为肺恶性肿瘤新的治疗方法,受到广泛关注。本研究旨在观察CT引导下CelonLab射频仪治疗兔肺内VX2肿瘤的影像学表现、病理演变,评价治疗效果,进一步探索肺恶性肿瘤的射频治疗参数。方法：采用同轴套管针经皮穿刺的新方法建立兔VX2肺肿瘤模型。实验组27只予以射频治疗,对照组9只予以假性治疗。两组均于设定时间点行CT扫描,观察影像学表现。实验组18只于治疗后不同时间点随机处死,观察病理演变;其余9只待其自然死亡,评估疗效、计算生存期。对照组9只均待其自然死亡,计算生存期。结果：射频后即刻CT扫描见病灶周围磨玻璃影可伴内部空洞或小空泡。与病理HE染色切片对照发现,术后随访中CT增强扫描无强化不能完全除外肿瘤细胞残留。术后24 h大体解剖见病灶由中心向外周形成4条沿能量梯度分布的反应带：中央炭化或蒸发中心(电极穿刺针道),灰白色凝固性坏死带,棕红色出血带,粉红色充血渗出带。术后肿瘤病灶周围出现不同程度炎性反应,4周后基本吸收,最终残留厚壁纤维组织层包绕中央凝固性坏死及少量陈旧性出血。实验组待其自然死亡的9只中,完全缓解率78%。实验组与对照组生存时间分别为(38.0±5.9) d与(24.0±3.1) d,差异有统计学意义(t=2.634,P=0.018)。射频能量与病灶直径之间存在直线回归关系,回归系数的检验P=0.000,直线回归方程为Y^=-2.3372+1.4361X。结论：采用同轴套管针经皮穿刺法建立兔VX2肺肿瘤模型安全、迅速,短期内成瘤率高。射频消融治疗肺内肿瘤疗效确切,安全、微创,并发症少。术后射频区域有一个发展演变的过程,疗效评估可以术后1个月为新基线。射频能量与病灶直径之间存在直线回归关系。     

经皮穿刺射频消融治疗兔肺内VX2肿瘤

目的　探讨CT引导下利用锚状电极射频消融治疗兔肺VX2肿瘤的病理改变、CT表现及治疗效果。方法　采用VX2肿瘤组织块悬液肺内注入法在 36只新西兰白兔体内建立兔VX2肿瘤肺内移植模型。实验组 2 8只新西兰白兔给予射频治疗 ,其中 14只于治疗后不同时间处死 ,观察其病理改变 ,并与同期CT表现相比较 ;其余 14只待其自然死亡 ,计算存活时间。对照组 8只新西兰白兔 ,予假性治疗 ,待其自然死亡 ,计算存活时间。结果　肿瘤经射频治疗后发生凝固性坏死及细胞凋亡 ,消融灶周围肺组织发生严重炎症反应 ;CT表现为絮状阴影 ,并随炎症的消散而消失 ,但肿瘤阴影不再增大。实验组 2 1只兔肺内毁损区肿瘤细胞全部灭活 ,7只毁损区有残存活肿瘤细胞。治疗组动物的存活时间为 ( 38± 3.4)天 ,对照组存活时间为 ( 2 6± 2 .8)天 (P <0 .0 5 )。结论　射频消融技术可望成为治疗肺内肿瘤的新方法。     

Two new tumor-specific antigenic peptides encoded by gene MAGE-C2 and presented to cytolytic T lymphocytes by HLA-A2

We have identified 2 antigens recognized by several melanoma-specific cytolytic T lymphocyte clones isolated from a melanoma patient with a clinical history of tumor regression after immunotherapy. Both antigens are presented by HLA-A2 and encoded by gene MAGE-C2, a cancer-germline gene shown previously to be silent in normal somatic tissues and expressed in 40% of melanomas and in other tumor types. One antigen corresponds to peptide ALKDVEERV(336-344), whereas the other corresponds to peptide LLFGLALIEV(191-200). The CTL clones recognizing these 2 peptides also recognized allogeneic tumor cell lines expressing MAGE-C2 and HLA-A2. These 2 new peptides are the first known MAGE-C antigens and represent promising targets for cancer immunotherapy.     

Activation of tumor-specific CD4(+) T lymphocytes by major histocompatibility complex class II tumor cell vaccines: a novel cell-based immunotherapy

Mouse tumor cells transfected with syngeneic MHC class II and costimulatory molecule genes are therapeutic vaccines in mice, provided they do not coexpress the class II-associated invariant chain (Ii). We demonstrated previously that the vaccine cells present tumor peptides via the endogenous antigen presentation pathway to activate CD4(+) and CD8(+) T cells. Because of their efficacy in mice, we are translating this vaccine strategy for clinical use. To obtain MHC class II(+)CD80(+)Ii(-) human tumor cells, we developed retroviruses encoding HLA-DR and CD80. The HLA-DR virus encodes the DRalpha and DRbeta0101 chains using an internal ribosomal entry site to coordinate expression. SUM159PT mammary carcinoma and Mel 202 ocular melanoma cells transduced with the retroviruses DRB1/CD80 express high levels of DRB0101 and CD80 on the cell surface in the absence of Ii. Irradiated SUM159PT/DR1/CD80 vaccines stimulate proliferation of non-HLA-DRB0101 peripheral blood mononuclear cells and present an exogenous DR1-restricted tetanus toxoid (TT) peptide, indicating that the transduced DRB0101 is functional. SUM159PT/DR1/CD80 vaccines were further transduced with a retrovirus encoding the TT fragment C gene, as a model tumor antigen. These cells stimulate IFN-gamma release from TT-primed human DRB0101 peripheral blood mononuclear cells, demonstrating their ability to present "endogenous" tumor antigen. Depletion and antibody blocking experiments confirm that MHC class II-restricted, endogenously synthesized epitopes are presented to CD4(+) T cells. Therefore, the MHC class II vaccines are efficient antigen-presenting cells that activate tumor-specific MHC class II-restricted, CD4(+) T lymphocytes, and they are a novel and potential immunotherapeutic for metastatic cancers.     

Distribution of autologous tumor-specific cytotoxic T lymphocytes in human metastatic melanoma.

The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma-specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non-visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T-cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor specific CTL clones were detected in 6 of 18 tumors (33%, 4 non-visceral and 2 visceral metastases). The majority of CTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class-I A2 haplotype failed to lyse either A2+ or A2- allogeneic melanoma cells, although anti-class-I (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2-restricted cytotoxicity. Autologous tumor-specific cytotoxicity was also detected after polyclonal culture of these tumor-infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non-visceral and 3 visceral metastases). These results suggest that tumor-specific T cells exist at tumor sites in at least one-third of distant metastases of melanomas and could be induced by the addition of IL-2 in at least half of the tumors. Tumor-specific T cells were detectable more often in non-visceral than in visceral metastases.     

Induction of tumor-specific cytotoxic T lymphocytes from regional lymph node lymphocytes of human breast cancer

Background  In this study we activated breast cancer-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes (RLNL) of HLA-A2-positive patients with breast cancer. Melthods  Freshly isolated RLNL were stimulated with solid phase anti-CD3 monoclonal antibody followed by expansion with recombinant interleukin-2. Subsequently, the RLNL were stimulated with an irradiated HLA 0201 breast cancer cell line, MCF-7, at a responder/stimulator ratio of 10/1 once a week for 2 weeks. Results  The cultured RLNL exhibited specific lysis against MCF-7 in all 5 HLA-A2-positive patients tested, but not in 2 HLA-A2-negative patients. Cytotoxicity against MCF-7 was substantially inhibited by addition of anti-HLA-A2 mAb. In 3 of 5 HLA-A2-positive patients, anti-MCF-7 CTL also exhibited a substantial level of reactivity against PC-9, an HLA-A0206-positive lung adenocarcinoma cell line. Conversely, anti-PC-9-specific CTL were inducible by multiple stimulations of RLNL with PC-9 cells in 2 of 3 patients. Conclusions  These results suggest that several common tumor antigens might exist among HLA-A2-positive breast cancers, some of which may be shared with lung adenocarcinomas.     

CT引导下多弹头射频治疗晚期肺癌

目的：探讨多弹头射频（radiofrequency,RF)治疗晚期肺癌的疗效。方法：22例晚期肺癌患者在CT引导下进行RF治疗。结果：经过RF治疗，大部分患者痛有不同程度的缓解，19例患者术后CT示肿瘤内部空洞形成。3个月后20例患者行CT检查， 肺部肿瘤有不同程度的缩小，其中CR1例，PR12例，MR4例，SD3例。结论：CT引导下RF治疗肺部晚期肿瘤是一种安全、有效的微创治疗手段。     

In vitro induction of potent tumor-specific cytotoxic T lymphocytes using TLR agonist-activated AML-DC

Dendritic cells (DCs) are recognized as key regulators of the immune system. Active DC immunization protocols are quickly obtaining interest as an alternative therapeutic approach in acute myeloid leukemia patients. Despite apparent progress in DC-based immunotherapy, some discrepancies were reported in generating potent DCs and their source. In addition to monocytes, DCs can be differentiated from leukemic blasts of acute myeloid leukemia (AML) patients (AML-DC) possessing the ability of stimulating anti-leukemic immune response. In this study, we differentiated peripheral blood blasts of 16 out of 20 AML patients in vitro in the presence of GM-CSF and IL-4 into immature AML-DC. Then, DCs matured using different combinations of Toll-like receptor (TLR) ligands to obtain functional DCs as demonstrated by cell morphology, immunophenotype, and functional activity. Autologous cytotoxic T cell induction of matured DCs was evaluated in four patients and compared with immature counterparts. Our results showed that although the TLR3 agonist (Poly I:C) has a synergistic effect on the TLR4 agonist (lipopolysaccharide, LPS), the addition of the TLR7/8 agonist (R848) is necessary to reinforce the effect of LPS or LPS?+?POLY(I:C) to produce efficient DCs with the higher level of IL-12 (30 to 90 times). Such DCs activate allogeneic T cells and effectively prime autologous cytotoxic T cells in vitro. In contrast, FSL-1 as a TLR2/6 agonist has a negative effect on LPS?+?Poly(I:C) and LPS?+?R848 to produce IL-12. Thus, DCs prepared using a maturation mixture including a TLR7/8 agonist may be used as a potential tool for DC-based immunotherapy purposes in leukemic patients.     

兔接种VX2肿瘤的18F-FDG PET/CT观察

目的：应用正电子发射断层显影术（positron emission tomography，PET）／CT研究免接种VX2肿瘤后，不同时间的18F-氟脱氧葡萄糖（18F—fluoro-2-deoxyglueose，18F—FDG）的代谢变化，以及不同接种部位肿瘤18F—FDG代谢的差异。方法：建立VX2兔肿瘤模型，干接种后第14和19天，行PET／CT显像，观察肿瘤生长与标准摄取值（standard uptake value，SUV）的变化：根据CT测量计算肿瘤体积，取SUVmax进行统计，并计算2h肿瘤滞留指数（retention index，RI）；观察肿瘤部位18F—FDG分布情况并行病理学检查，分析各组肿瘤在不同时间的体积与SUV的相关性。结果：连续动态PET／CT观察发现，VX2肿瘤生长迅速，肿瘤体积随接种时间延长逐渐增加，各组SUV随接种时间延长均呈线性升高；组间比较。不同时间点肿瘤体积（r=0．89，P〈0．05）与SUV值（r=0．93，P〈0．05）呈显著相关，RI在不同时间点的差异无统计学意义（P〉0．05）；组内比较，不同时间点的SUV值与肿瘤体积无明显相关性（P〉0．05）。PET／CT和膦屏所见18F—FDG浓聚部位，经病理证实为肿瘤细胞富集区域。结论：VX2兔肿瘤模型是可用于PET／CT领域的理想动物模型；于不同部位接种，肿瘤的生长和侵袭方式相似；应用PET／CT进行放、化疗的疗效监测时，应选择在肿瘤18F—FDG代谢呈线性升高时间段进行。     

腹腔镜引导定位肝脏肿瘤射频消融治疗的临床观察

目的:探讨腹腔镜直视引导定位下肝癌射频热凝消融治疗(radio-ferquency ablation, RFA)的可行性.方法:在腹腔镜直视引导定位下分别对10例原发性肝癌和多发转移性肝癌进行一次性射频消融治疗.结果:10例患者28个瘤体中直径＜5 cm的20个肿瘤均获得一次性热凝损毁,其中18个瘤体完全缓解CR 90.0%(18/20),2个瘤体部分缓解PR 10.0%(2/20),近期疗效CR+PR为100.0%(20/20),1例术后15个月肝、肺转移复发;8个直径5～9 cm的瘤体近期疗效为CR+PR 100.0%(8/8),CR 50.0%(4/8),PR 50.0%(4/8),1例术后6个月发生肝门部转移及阻塞性黄疸而病情进展死亡,1例术后14个月因肝脏、肺脏广泛转移死亡.术后2周复查AFP、CEA和CA19-9等肿瘤标志均有不同程度的下降或转阴.所有患者均很好地耐受了射频消融治疗,无严重并发症出现.9例患者术后分别行1～4次肝动脉化疗栓塞介入治疗(TACE).1年生存率为85.7%(6/7),2年生存率为50.0%(3/6). 结论:腹腔镜直视引导定位下肝癌射频消融治疗为不能手术的原发性肝癌及多发性肝转移癌提供了一种微创、安全、有效、方便的治疗方法,与TACE结合效果更佳.     

Critical impact of the kinetics of dendritic cells activation on the in vivo induction of tumor-specific T lymphocytes

Dendritic cells (DCs) need activation for the priming of antigen-specific immune responses. Recently activated DCs were described to prime in vitro strong T helper cell type 1 (Th(1)) responses, whereas at later time points, the same cells preferentially prime Th(2) cells [Langenkemp, A. et al., Nat. Immunol. 1: 311-316, 2000]. Because the immune response against cancer strongly depends on CTLs of Th(1)-like phenotype (Tc(1)), we verified here whether the kinetics of DCs activation also impacted on in vivo priming of tumor-specific CTLs. After pulsing with the CTL epitope TRP-2(180-188), bone-marrow-derived DCs, exposed to lipopolysaccharide (LPS) for 8 h (8hDC), elicited a more powerful Tc(1) response in C57BL/6 mice than did untreated DCs, or DCs exposed to LPS for 48 h (48hDC). Indeed, 8hDCs were the most potent protective and therapeutic vaccine against B16 melanoma. Despite a higher expression of MHC and costimulatory molecules by 48hDCs, 8hDCs and 48hDCs showed comparable allostimulatory and migration potential, and susceptibility to CTL-mediated apoptosis. However, 8hDCs exhibited a significantly higher interleukin (IL)-12 production potential. Release of IL-12 was necessary to induce potent Tc(1) cells, because DCs from IL-12p40(-/-) mice, irrespective of their maturation level, generated low CTL responses, comparable with 48hDCs and 0hDCs from wild-type animals. Our data are relevant for the design of DC-based vaccines.     

Identification of cyclophilin B-derived peptides capable of inducing histocompatibility leukocyte antigen-A2-restricted and tumor-specific cytotoxic T lymphocytes.

We recently suggested that cyclophilin B (Cyp-B) is a tumor antigen recognized by histocompatibility leukocyte antigen (HLA)-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). In this study, we tried to identify Cyp-B-derived epitopes, which can induce HLA-A2-restricted and tumor-specific CTLs in cancer patients. The tumor-infiltrating lymphocytes (TILs) from an HLA-A0207 patient with colon cancer were found to respond to COS-7 cells when co-transfected with the Cyp-B gene and either HLA-A0201, -A0206, or -A0207 cDNA. These TILs contained CTLs capable of recognizing either the Cyp-B(129 - 138) or the Cyp-B(172 - 179) peptide among 28 different peptides, all of which were prepared based on the HLA-A2 binding motif. Both Cyp-B peptides possessed the ability to induce tumor-specific CTLs in HLA-A2(+) cancer patients. Cyp-B(172 - 180 (V)), which is a 9-mer peptide with valine added at the C terminus, showed no clear superiority over the parental Cyp-B(172 - 179) peptide in an in vitro sensitization experiment. In vitro-sensitized T cells with these peptides responded to cancer cells in an HLA-A2-restricted manner. These two Cyp-B peptides could be useful for specific immunotherapy of HLA-A2(+) cancer patients.     

Selective effect of doxorubicin suspended in lipiodol on VX2 carcinoma in rabbits

When Lipiodol Ultra-Fluid (Lipiodol) was given through arteries feeding the tumor, this material was retained in the tumor. After mixing Lipiodol and doxorubicin (adriamycin; ADR), the effect of this antitumor agent on VX2 carcinoma inoculated into the hindlimb in 57 rabbits was investigated. Size of the tumor remarkably decreased in the rabbits treated with ADR 2 mg/kg suspended in Lipiodol and given through the femoral artery. Intraarterial injection of ADR 2 mg/kg alone led to a transient decrease in size of the tumor, but there was a regrowth. The result was comparable to a finding in a group in which half the dose of ADR (1 mg/kg) suspended in Lipiodol was given intraarterially. When ADR 2 mg/kg mixed with Lipiodol was injected directly into the tumor, growth of the tumor was not completely inhibited. Lipiodolized ADR has a prominent antitumor effect, and Lipiodol has the potential to be applied as a carrier of anticancer drugs.     

CT引导下经皮无水乙醇消融兔肾VX2肿瘤的实验研究

背景与目的:CT引导下经皮无水乙醇消融(pereutaneous ethanol ablation,PEA)在肝癌、肺癌及肾上腺无功能腺瘤等实体肿瘤的治疗中得到广泛应用,但目前有关经皮无水乙醇消融治疗肾脏实体肿瘤的实验及临床应用仍未见报道.本研究通过CT引导下经皮无水乙醇消融兔肾VX2肿瘤,探讨无水乙醇消融治疗肾脏肿瘤的有效性、安全性和可行性.方法:将25只已建立兔肾VX2肿瘤的新西兰大白兔随机分为治疗组15只和对照组10只.治疗组行CT引导下经皮无水乙醇消融并测量碘油沉积区致密影最大截面面积.对照组不接受治疗.1周后取出两组兔荷瘤肾脏,测量两组肿瘤大小及治疗组肿瘤凝固坏死区最大截面面积.对比观察实验兔治疗后伤口有无感染及生活习性的改变.结果:25只兔共形成25个肾脏肿瘤,最大截面积为1.38～2.25 cm2,平均(1.61～0.04)cm2,两组肿瘤大小差异无统计学意义(P>0.05).治疗组经皮无水乙醇消融后,碘油沉积面积大小1.31～1.85 cm2,平均(1.56±0.05)cm2;PEA治疗1周后,治疗组肿瘤大小1.35～1.85 cm2,平均(1.58±0.03)cm2,对照组肿瘤大小1.67～2.17 cm2,平均(1.94±0.03)cm2,两组对比差异有统计学意义(P<0.05).治疗组肿瘤凝固坏死区面积大小1.27～1.78 cm2,平均(1.54±0.04)cm2,与碘油沉积面积比较,差异无统计学意义(P>0.05).消融区肿瘤组织呈嗜酸性改变及不规则片状凝固性坏死.治疗组动物均未出现明显不良反应及并发症.结论:CT引导下经皮无水乙醇消融可有效灭活兔肾VX2肿瘤组织;CT引导下经皮无水乙醇消融兔肾VX2肿瘤无明显不良反应及并发症.安全可行.     

Probucol decreases total body fat loss in VX2-carcinoma-induced cachectic rabbits

We previously reported the continuous decrease of total body fat in VX2-carcinoma-bearing rabbits after tumor implantation, as well as changes in the serum lipid profile. Probucol, an antioxidant drug, has a cholesterol lowering effect against hyperlipidemic subjects. VX2-carcinoma-bearing rabbits fed with a diet containing 1% probucol did not show any difference in serum lipid compositions as compared with rabbits fed with a control diet. Similarly serum lipolytic activity showed no differences, whether probucol was administered or not, while the decrease in total body fat was significantly less when probucol was administered.     

Tissue-specific pharmacodynamics of 5-bromo-2'-deoxyuridine incorporation into DNA in VX2 tumor-bearing rabbits

The thymidine analog 5-bromo-2'-deoxyuridine (BrdUrd) is felt to exert its cytotoxic effects primarily through incorporation into DNA. We have evaluated the incorporation of BrdUrd into the DNA of relevant normal tissues (bone marrow, gut mucosa, and liver) and tumor in rabbits with the VX2 tumor growing intrahepatically. Using constant i.v. infusions, steady state plasma drug concentrations ranging from 0.4 to 65.4 microM were maintained for 24 h and tissues were harvested and processed so that a sensitive gas chromatography/mass spectrometry (GC/MS) method could be used to analyze the thymine and 5-bromouracil content of hydrolyzed DNA. In all tissues, DNA incorporation showed saturating effects as plasma BrdUrd concentration was increased and, BrdUrd incorporation as a function of plasma concentration could be fitted to a Langmuir-like equation generating tissue-specific pharmacodynamic parameters: Imax for percentage thymine replacement at infinite plasma BrdUrd concentrations, and C50 for the arterial BrdUrd concentration generating incorporation that is Imax/2. At all plasma concentrations of BrdUrd the incorporation into DNA of bone marrow was greater than that observed in VX2 tumor. However, BrdUrd labeling index (with a BrdUrd monoclonal antibody) was greater in tumor than bone marrow. Thus, pharmacodynamic differences in incorporation do not result solely from cytokinetic differences between tissues. This model may prove useful in evaluating the pharmacodynamics of incorporation in studies using hepatic arterial infusion and biochemical modulation to improve selectivity.     

兔VX2食管癌模型的建立及生物学特性观察

目的:建立兔VX2食管癌移植瘤模型,探讨其成瘤率、生长特性及转移情况,为进一步研究食管癌及寻找有效治疗方法提供平台.方法:将兔VX2肿瘤剪碎至1 mm3左右的组织块,通过外科手术将肿瘤块植入腹段食管黏膜下层,于接种后第1、2及3周分别行食管造影和CT扫描检查,观察肿瘤生长情况.3周后,处死兔子取标本行病理学检测.结果:12只兔子除2只死于手术并发症外(胃穿孔及误缝食管所致的梗阻),其余10只接种后1周,未见肿瘤生长;2周后食管造影显示食管下段充盈缺损.CT扫描示食管下段走行区局限性管壁增厚,有明显软组织肿块影,平均最大径为1.04 cm (0.7～1.5 cm);3周后兔子消瘦明显,食管造影示食管下段黏膜破坏,充盈缺损明显,4只兔子出现食管穿孔.CT扫描示食管下段软组织肿块影明显增大,平均最大径为2.28 cm (1.7～4.3 cm).瘤体及淋巴结病理检查证实,成瘤及淋巴结转移成功率为100%.结论:采用兔VX2瘤块移植法可成功建立食管癌移植模型,且具有周期短,成瘤率高,生长迅速等特点.     

Antitumor effect of curcumin liposome after transcatheter arterial embolization in VX2 rabbits

Background: Hypoxia may affect the therapeutic efficacy of transcatheter arterial embolization (TAE), which is widely used in nonsurgical hepatocellular carcinoma (HCC). Liposomal curcumin can exert anticancer effect. Our purpose is to explore the antitumor effect of liposomal curcumin on the HCC after TAE.

Methods: The HepG2 cells were cultured under hypoxic condition (1% O₂) and then treated with curcumin liposome. Cell viability, apoptosis and cell cycle were respectively measured by CCK-8 and a flow cytometry. The VX2 rabbits were randomly distributed into three groups: control group with saline embolization, TAE group with lipiodol embolization and curcumin liposome group with curcumin liposome and lipiodol embolization. MRI and CT perfusion scanning were performed after embolization. The hepatocyte apoptosis was measured by the terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL). The vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured by immunohistochemical. RT-PCR and Western blot were performed to examine mRNA and protein levels.

Results: By regulating the apoptosis-related molecules, curcumin liposome obviously inhibited the cell viability and promoted the apoptosis in G1 phase. Curcumin liposome reduced the tumor size and alleviated neoplasia in VX2 rabbits. Curcumin liposome decreased the expressions of MVD and VEGF and increased the apoptosis of liver tissues. The levels of hypoxia-inducible factor-1α (HIF-1α) and survivin were suppressed by curcumin liposome both in hypoxic cells and liver tissues in the VX2 rabbits.

Conclusion: Curcumin liposome exerted antitumor effect by regulating the proliferation- and apoptosis-related molecules. Curcumin liposome suppressed the HIF-1α and survivin levels and inhibited the angiogenesis in VX2 rabbits after TAE.